Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study

doi:10.1007/s00415-022-11253-1

. 2022 Dec;269(12):6354-6365.

doi: 10.1007/s00415-022-11253-1. Epub 2022 Jul 23.

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study

T Bogdan^#¹, T Wirth^#^{2

3

4}, A Iosif², A Schalk^{3

5}, S Montaut², C Bonnard², G Carre², O Lagha-Boukbiza², C Reschwein², E Albugues², S Demuth², H Landsberger², M Einsiedler², T Parratte², A Nguyen², F Lamy², H Durand², P Fahrer², P Voulleminot², K Bigaut², J B Chanson², G Nicolas⁶, J Chelly⁵, C Cazeneuve⁷, M Koenig⁸, C Bund^{9

10}, I J Namer^{9

10}, S Kremer¹¹, N Calmels⁵, C Tranchant^{2

3

4}, M Anheim^{2

3

4}

Affiliations

¹ Neurology Department, Strasbourg University Hospital, Strasbourg, France. thomas.bogdan@chru-strasbourg.fr.
² Neurology Department, Strasbourg University Hospital, Strasbourg, France.
³ Strasbourg Federation of Translational Medicine (FMTS), Strasbourg University, Strasbourg, France.
⁴ INSERM-U964; CNRS-UMR7104, University of Strasbourg, Illkirch-Graffenstaden, France.
⁵ Laboratory of Genetic Diagnosis, IGMA, Strasbourg University Hospital, Strasbourg, France.
⁶ Department of Genetics and CNRMAJ, FHU G4 Génomique, Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, 76000, Rouen, France.
⁷ Neurogenetics Laboratory, Department of Genetics, APHP, University Hospital Pitié-Salpêtrière, Paris, France.
⁸ Laboratory of Molecular Genetics, Montpellier University Hospital, Montpellier, France.
⁹ Department of Nuclear Medicine, Strasbourg University Hospital, Strasbourg, France.
¹⁰ Department of Nuclear Medicine and Molecular Imaging, ICANS, Strasbourg, France.
¹¹ Department of Radiology, Strasbourg University Hospital, Strasbourg, France.

^# Contributed equally.

PMID: 35869996
DOI: 10.1007/s00415-022-11253-1

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study

T Bogdan et al. J Neurol. 2022 Dec.

. 2022 Dec;269(12):6354-6365.

doi: 10.1007/s00415-022-11253-1. Epub 2022 Jul 23.

Authors

Affiliations

¹ Neurology Department, Strasbourg University Hospital, Strasbourg, France. thomas.bogdan@chru-strasbourg.fr.
² Neurology Department, Strasbourg University Hospital, Strasbourg, France.
³ Strasbourg Federation of Translational Medicine (FMTS), Strasbourg University, Strasbourg, France.
⁴ INSERM-U964; CNRS-UMR7104, University of Strasbourg, Illkirch-Graffenstaden, France.
⁵ Laboratory of Genetic Diagnosis, IGMA, Strasbourg University Hospital, Strasbourg, France.
⁶ Department of Genetics and CNRMAJ, FHU G4 Génomique, Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, 76000, Rouen, France.
⁷ Neurogenetics Laboratory, Department of Genetics, APHP, University Hospital Pitié-Salpêtrière, Paris, France.
⁸ Laboratory of Molecular Genetics, Montpellier University Hospital, Montpellier, France.
⁹ Department of Nuclear Medicine, Strasbourg University Hospital, Strasbourg, France.
¹⁰ Department of Nuclear Medicine and Molecular Imaging, ICANS, Strasbourg, France.
¹¹ Department of Radiology, Strasbourg University Hospital, Strasbourg, France.

^# Contributed equally.

PMID: 35869996
DOI: 10.1007/s00415-022-11253-1

Abstract

Background: Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations.

Methods: We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations.

Results: We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01).

Conclusion: Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

Keywords: Brain MRI; Genetics; I123-ioflupane SPECT; Late-onset cerebellar ataxia; Multiple system atrophy.

PubMed Disclaimer

Cited by

Does Spinocerebellar ataxia 27B mimic cerebellar multiple system atrophy?
Wirth T, Bonnet C, Delvallée C, Pellerin D, Bogdan T, Clément G, Schalk A, Chanson JB, Fleury MC, Piton A, Calmels N, Namer IJ, Kremer S, Brais B, Tranchant C, Renaud M, Anheim M. Wirth T, et al. J Neurol. 2024 Apr;271(4):2078-2085. doi: 10.1007/s00415-024-12182-x. Epub 2024 Jan 23. J Neurol. 2024. PMID: 38263489
Comprehensive Evaluation of Sporadic Late-Onset Cerebellar Ataxias: Clinical Presentation, Diagnostic Challenges, and Treatment Outcomes.
Barbouch I, Ali Kako A, Mebrouk Y. Barbouch I, et al. Cureus. 2024 Jun 19;16(6):e62667. doi: 10.7759/cureus.62667. eCollection 2024 Jun. Cureus. 2024. PMID: 39036235 Free PMC article.
Spinocerebellar ataxia 27B: A novel, frequent and potentially treatable ataxia.
Pellerin D, Danzi MC, Renaud M, Houlden H, Synofzik M, Zuchner S, Brais B. Pellerin D, et al. Clin Transl Med. 2024 Jan;14(1):e1504. doi: 10.1002/ctm2.1504. Clin Transl Med. 2024. PMID: 38279833 Free PMC article. Review.
Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B.
Bonnet C, Pellerin D, Roth V, Clément G, Wandzel M, Lambert L, Frismand S, Douarinou M, Grosset A, Bekkour I, Weber F, Girardier F, Robin C, Cacciatore S, Bronner M, Pourié C, Dreumont N, Puisieux S, Iruzubieta P, Dicaire MJ, Evoy F, Rioux MF, Hocquel A, La Piana R, Synofzik M, Houlden H, Danzi MC, Zuchner S, Brais B, Renaud M. Bonnet C, et al. Sci Rep. 2023 Jun 15;13(1):9737. doi: 10.1038/s41598-023-36654-8. Sci Rep. 2023. PMID: 37322040 Free PMC article.
The Frequency of Intermediate Alleles in Patients with Cerebellar Phenotypes.
Capacci E, Bagnoli S, Giacomucci G, Rapillo CM, Govoni A, Bessi V, Polito C, Giotti I, Brogi A, Pelo E, Sorbi S, Nacmias B, Ferrari C. Capacci E, et al. Cerebellum. 2024 Jun;23(3):1135-1145. doi: 10.1007/s12311-023-01620-7. Epub 2023 Oct 31. Cerebellum. 2024. PMID: 37906407 Free PMC article.

References

1. Mahlknecht P, Kiechl S, Bloem BR et al (2013) Prevalence and burden of gait disorders in elderly men and women aged 60–97 years: a population-based study. PLoS ONE 8:e69627. https://doi.org/10.1371/journal.pone.0069627 - DOI - PubMed - PMC
1. Muzaimi MB (2004) Population based study of late onset cerebellar ataxia in south east Wales. J Neurol Neurosurg Psychiatry 75:1129–1134. https://doi.org/10.1136/jnnp.2003.014662 - DOI - PubMed - PMC
1. Klockgether T (2010) Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 9:94–104. https://doi.org/10.1016/S1474-4422(09)70305-9 - DOI - PubMed
1. Cortese A, Simone R, Sullivan R et al (2019) Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet 51:649–658. https://doi.org/10.1038/s41588-019-0372-4 - DOI - PubMed - PMC
1. Pfeffer G, Pyle A, Griffin H et al (2015) SPG7 mutations are a common cause of undiagnosed ataxia. Neurology 84:1174–1176. https://doi.org/10.1212/WNL.0000000000001369 - DOI - PubMed - PMC

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
- Springer

[1] Mahlknecht P, Kiechl S, Bloem BR et al (2013) Prevalence and burden of gait disorders in elderly men and women aged 60–97 years: a population-based study. PLoS ONE 8:e69627. https://doi.org/10.1371/journal.pone.0069627 - DOI - PubMed - PMC

[2] Mahlknecht P, Kiechl S, Bloem BR et al (2013) Prevalence and burden of gait disorders in elderly men and women aged 60–97 years: a population-based study. PLoS ONE 8:e69627. https://doi.org/10.1371/journal.pone.0069627 - DOI - PubMed - PMC

[3] Muzaimi MB (2004) Population based study of late onset cerebellar ataxia in south east Wales. J Neurol Neurosurg Psychiatry 75:1129–1134. https://doi.org/10.1136/jnnp.2003.014662 - DOI - PubMed - PMC

[4] Muzaimi MB (2004) Population based study of late onset cerebellar ataxia in south east Wales. J Neurol Neurosurg Psychiatry 75:1129–1134. https://doi.org/10.1136/jnnp.2003.014662 - DOI - PubMed - PMC

[5] Klockgether T (2010) Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 9:94–104. https://doi.org/10.1016/S1474-4422(09)70305-9 - DOI - PubMed

[6] Klockgether T (2010) Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 9:94–104. https://doi.org/10.1016/S1474-4422(09)70305-9 - DOI - PubMed

[7] Cortese A, Simone R, Sullivan R et al (2019) Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet 51:649–658. https://doi.org/10.1038/s41588-019-0372-4 - DOI - PubMed - PMC

[8] Cortese A, Simone R, Sullivan R et al (2019) Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet 51:649–658. https://doi.org/10.1038/s41588-019-0372-4 - DOI - PubMed - PMC

[9] Pfeffer G, Pyle A, Griffin H et al (2015) SPG7 mutations are a common cause of undiagnosed ataxia. Neurology 84:1174–1176. https://doi.org/10.1212/WNL.0000000000001369 - DOI - PubMed - PMC

[10] Pfeffer G, Pyle A, Griffin H et al (2015) SPG7 mutations are a common cause of undiagnosed ataxia. Neurology 84:1174–1176. https://doi.org/10.1212/WNL.0000000000001369 - DOI - PubMed - PMC

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study

Affiliations

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study

Authors

Affiliations

Abstract

Similar articles

Cited by

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Abstract

Similar articles

Cited by

References

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources